Manuel francisco allende

It was on the occasion of my first visit to San Francisco that I got to know Manuel Frank Allende. He was born in Uruguay in 1918 but spent time in Paris where he worked as a hospital registrar shortly before the war. In 1940, he saw the occupation of France by the Germans. He passed over the Spanish border, was briefly interned and then set off back to the United States. He had a brief "stay" at Ellis Island opposite Manhattan, before obtaining a resident's permit enabling him to continue his speciality, dermatology. He then left for California, his wife, Katharine's home state. Manuel Frank was very open-minded, benefiting from the Spanish, French and American cultures, a "man of the world" before the term had been invented. We soon got on well, he liked skiing, which he had practised in Alpe d'Huez before the war. I visited him in San Francisco where he lived in a house dominating the Bay near the Golden Gate. He drew and painted the wonderful view he had from his windows. He died suddenly on the slopes in the Rocky Mountains. Katharine still lives in San Francisco where she has long been a member of the governing body of the French hospital. Manuel Frank left a marvellous collection of drawings which illustrate well the kind of man he was.

Stefanie jablonska, the iron lady of warsaw

Among the founders of immuno-dermatology, a prominent place is occupied by Stefanie Jablonska, Professor of Dermatology in Warsaw. Despite all the difficulties which her country has known, she has been able to work, train many students, travel the whole world over and survive all the crises. She is always on the go and the years have left no mark on her. From the time of my nomination as Professor of Dermatology I had occasion to see her at the Hopital St-Louis where the monthly meetings united many French and foreign dermatologists. From our first contact we got on well. She attended certain of my lectures, criticized with interest and supported the beginnings of my career. She believed that dermatology could no longer be content with clinical description, which was where the French reputation in dermatology lay. It was now necessary to give a larger role to biological research. And this is what I tried to do in adding a research laboratory to the clinical service I directed.

External anogenital lesions in organ transplant recipients. A clinicopathologic and virologic assessment.

BACKGROUND AND DESIGN: In a series of patients treated at a university department of dermatology, we assessed the clinicopathologic features of external anogenital lesions in organ transplant recipients. For 6 years, 1002 recipients with various dermatologic problems underwent assessment for the presence of proliferative external anogenital lesions; these lesions were examined histologically and virologically for the presence of human papillomaviruses (HPV). RESULTS: Twenty-three patients (2.3%) presented with anogenital lesions, women being more often involved. Clinicopathologic examination revealed 18 anogenital warts, 3 cases of bowenoid papulosis, 1 giant condyloma, and 1 in situ carcinoma. Other viral coinfections were frequent. The lesions were extensive and refractory to treatment in 13 patients, but lesions in 7 were cured alter the immunosuppressive treatment was tapered of discontinued. Dysplastic changes were frequent on histologic examination. Twenty-one lesions contained HPV; 6 of 13 patients with HPV DNA in their lesions harbored oncogenic types that predominated in dysplastic lesions. In some patients, the same HPV types were detected within cutaneous and anogenital lesions, suggesting self-contamination. CONCLUSIONS: External anogenital lesions are more rare than cutaneous lesions in organ transplant recipients. These lesions may represent a marker of immunosuppression, especially when they are extensive. Their clinical aspect is often misleading; furthermore, because of the presence of dysplastic histologic aspects and oncogenic HPV types, they could be susceptible to malignant transformation, necessitating regular surveillance.

Retinoids for the management of dermatological complications of organ transplantation.

Organ transplant recipients receiving immunosuppressive therapy are prone to skin cancers, especially squamous cell carcinomas on sun-exposed areas. The frequency of skin cancers increases with time after transplantation, reaching 40 to 70% of patients after 20 years. Squamous cell carcinomas tend to be multiple and may have a life-threatening course. They are often associated with warts, premalignant keratoses, Bowen's disease and keratoacanthomas. Repeated excisions of tumours and sessions of cryotherapy are not always satisfactory, as they lead to numerous scars and aesthetic impairment. Systemic retinoids may be used in organ transplant recipients without inducing graft rejection; they prevent the occurrence of dysplastic lesions and skin carcinomas. There is usually relapse following discontinuation of retinoids, raising the question of continuous or intermittent treatment. The long term use of retinoids may be limited by adverse effects which are cumulative with those of immunosuppressive treatment. Hence, systemic retinoids should be reserved for patients developing a great number of lesions over short periods. Topical retinoids probably represent the best way to control the proliferation of premalignant and malignant lesions. Further studies are required to assess the efficacy and safety of new retinoids.

[Malignant syphilis in human immunodeficiency virus infection]. / Syphilis maligne au cours de l'infection par le virus de l'immunodéficience humaine.

INTRODUCTION: The associated infection with Treponema pallidum and human immunodeficiency virus (HIV) was responsible for the return of malignant syphilis. CASE REPORT: We report a case of malignant syphilis which revealed a HIV seropositivity. The lesions were typical. Serological features were in accordance with the diagnosis. A treatment with penicillin was prescribed and there was no relapse after five years. DISCUSSION: The diagnosis of malignant syphilis in a HIV positive patient may be difficult. The course of the disease may be serious and a prolonged treatment with high doses of penicillin is often necessary. The occurrence of the malignant syphilis in HIV positive patients is not fortuitous and seems to be related to an abnormal immunity.

Comparative epidemiologic study of premalignant and malignant epithelial cutaneous lesions developing after kidney and heart transplantation.

BACKGROUND: Cutaneous carcinomas are the most frequent cancers in organ transplant recipients. OBJECTIVE: Our purpose was to compare the epidemiologic data of cutaneous premalignant and malignant epithelial lesions in kidney and heart transplant recipients. METHODS: A total of 580 kidney and 150 heart transplant recipients were examined for the presence of premalignant and malignant epithelial lesions. RESULTS: A twofold increase in incidence of premalignant and malignant epithelial lesions was found in heart compared with kidney transplant recipients. Heart transplant recipients were older at transplantation, received more intense immunosuppressive treatment, and had a shorter delay from transplantation to the development of the first lesion. The squamous cell carcinoma/basal cell carcinoma ratio was 2.37:1 in kidney and 1.08:1 in heart transplant recipients. The extracephalic location represented 60% of the premalignant and malignant epithelial lesions in kidney and 30% in heart transplant recipients. CONCLUSION: Cutaneous premalignant and malignant epithelial lesions in kidney and heart transplant recipients show epidemiologic differences that can tentatively be explained by the older age and the more intense immunosuppressive treatment of heart transplant recipients.

Major antigenic epitopes of bullous pemphigoid 230 kDa antigen map within the C-terminal end of the protein. Evidence using a 55 kDa recombinant protein.

In order to obtain greater insight into the nature of B-cell epitopes in bullous pemphigoid (BP), we generated a BP recombinant protein of 55 kDa M(r) (rBP 55) from a cDNA sequence encoding for the carboxyterminal region of the 230 kDa BP antigen. Serum IgG from guinea-pigs immunized with rBP 55 stained the basement membrane zone of normal human skin and immunoprecipitated the rBP 55 protein, and also the 230 kDa BP antigen recovered from extracts of cultured keratinocytes, thus confirming that the rBP 55 amino acid sequence is present in native BP antigen. The reactivity of sera from 60 patients with BP was analysed using an immunoblot assay on epidermal protein extracts and on the rBP 55 protein. Forty of the 60 BP sera (66%) contained autoantibodies to the 230 kDa polypeptide in an epidermal extract, and 37 of these 40 sera (92%) recognized the rBP 55 protein. In contrast, no reactivity against rBP 55 was detected with 20 BP sera devoid of autoantibodies against the 230 kDa antigen. Likewise, sera from patients with autoimmune blistering skin disorders other than BP (epidermolysis bullosa acquisita or pemphigus vulgaris), and control sera, were unreactive to rBP 55. These results clearly demonstrate the immunogenicity and antigenicity of the C-terminal end of the 230 kDa BP antigen. They confirm that this 555 amino acid segment, corresponding to rBP 55, contains major epitopes which can bind BP patients' autoantibodies, and suggest that the rBP 55 protein could be useful for further characterization of these B-cell epitopes.

Human monoclonal autoantibodies specific for the bullous pemphigoid antigen 1 (BPAg 1).

Bullous pemphigoid (BP) is an acquired blistering skin disease associated with the production of IgG autoantibodies to the 230-kDa BP Ag (BPAg1). To better characterize the epitopes of BPAg1, we generated immortalized B cell lines secreting human mAbs (HumAbs) to BPAg1 from two BP patients whose sera reacted with native BPAg1 but not with a recombinant BP55 carboxyl-terminal peptide. Ab-producing B cell lines were established by EBV infection of CD40-activated PBMCs. Three independent clonal lines were obtained that secreted IgG HumAbs, including one IgG1 kappa (BP3) and two distinct IgG4 kappa (BP1 and BP2). These three HumAbs immunoprecipitated BPAg1. Blocking immunofluorescence experiments and phylogenetic studies showed that these Abs recognize different epitopes of BPAg1. This analysis with HumAbs further extends the serologic demonstration of the wide variety of epitopes recognized by BPAg1 autoantibodies which contrasts with the limited number of epitopes recognized by thyroid peroxidase monoclonal autoantibodies.

Disseminated superficial porokeratosis in a patient with AIDS.

We report the case of a 50-year-old male homosexual suffering from AIDS, who developed diffuse annular hyperkeratotic lesions on the arms and legs. Histopathological examination revealed typical features of porokeratosis, which clinically was of the disseminated superficial type. Ultrastructural examination showed a paucity of keratohyalin granules and lamellar bodies. Immunohistochemical studies showed an almost complete absence of Langerhans cells in lesional epidermis. Involucrin and filaggrin expression were altered in areas of cornoid lamella formation, whereas basal keratinocytes in these areas expressed PCNA/cyclin and, to a lesser degree, p53 protein. Porokeratosis may affect immunocompetent patients, but has also been reported in the setting of immunosuppression following organ transplantation. As far as we are aware, the development of porokeratosis during the course of HIV infection has not been reported previously.

A novel therapeutic approach to psoriasis with combination calcipotriol ointment and very low-dose cyclosporine: results of a multicenter placebo-controlled study.

BACKGROUND: Recent advances in the treatment of psoriasis include both the topical vitamin D analogue calcipotriol and cyclosporine. Combined treatments have been sought to decrease the incidence of side effects while maintaining efficacy in the treatment of severe chronic plaque psoriasis. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of the combination of 2 mg/kg/day of cyclosporine with calcipotriol ointment (50 micrograms/gm) in the treatment of severe plaque psoriasis. METHODS: Sixty-nine patients were randomly selected for this double-blind, multicenter study to receive cyclosporine (2 mg/kg/day) combined with calcipotriol ointment (50 micrograms/gm) or cyclosporine (2 mg/kg/day) combined with placebo ointment (vehicle of calcipotriol) for a 6-week period. RESULTS: Complete clearing or 90% improvement in Psoriasis Area and Severity Index score occurred in 50.0% of patients in the calcipotriol/cyclosporine group in comparison with 11.8% of patients treated with placebo/cyclosporine (p = 0.0019). The confidence interval for the difference ranged from 17.8% to 58.7%. No difference was found between the two groups with respect to side effects. CONCLUSION: The calcipotriol/cyclosporine combination was more effective than placebo/cyclosporine. Further studies are needed to establish the long-term efficacy and safety profile of this combination therapy.

Potentializing effect of ketoconazole on cyclosporin A-induced inhibition of keratinocyte DNA synthesis.

Keratinocyte growth in vitro and DNA synthesis by epidermal cells in vivo are inhibited by therapeutic doses of cyclosporin A (CsA). This effect may be potentialized by topical treatment with ketoconazole, since this drug has been shown to inhibit CsA metabolism. Normal human skin grafts on nude mice receiving intraperitoneal injections of CsA were treated with ketoconazole cream or its placebo for 3 weeks. The keratinocyte DNA synthesis rate was evaluated through the rates of bromodeoxyuridine (BrdU) incorporation, and the trough blood levels of CsA were checked at the end of the experiment. Counting of the BrdU-labelled nuclei in human tissue sections confirmed a dose-dependent inhibition of BrdU incorporation by keratinocytes exposed to CsA. This CsA-induced inhibition was further increased in the animals treated with ketoconazole cream. This effect was best seen in the groups treated with the low-to-medium doses of CsA (12.5 and 25 mg/kg/day). However, the simultaneous increase in the circulating CsA levels was also observed in these animals. Based on our results, we speculate that the potentializing effect of ketoconazole on CsA-induced inhibition of keratinocyte DNA synthesis is systemic rather than local.